Cottrell D A, Blakely E L, Johnson M A, Borthwick G M, Ince P I, Turnbull D M
Department of Neurology, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH.
Novartis Found Symp. 2001;235:234-43; discussion 243-6. doi: 10.1002/0470868694.ch19.
The chronological accumulation of mitochondrial DNA mutations has been proposed as a potential mechanism in the physiological processes of ageing and age-related disease. We discuss the evidence behind this theory and relate some of the ageing mitochondrial changes to mitochondrial DNA disorders. In particular, we describe the aggregation of cytochrome c oxidase-deficient cells in both skeletal muscle and the CNS in normal ageing as seen in the mitochondrial DNA disorders. These mitochondrial enzyme-deficient cells have been shown to occur in significant quantities in both muscle and CNS in patients with mitochondrial DNA disorders. In both ageing and mtDNA disorder muscle these cytochrome c-deficient fibres contain high levels of a single mutant strain of mitochondrial DNA. Whether these mutations are a primary or secondary event in the physiology of ageing remains to be determined.
